Group B Streptococcus (GBS) afflicts about 8,000 newborns and 18,000 people in the United States annually. It represents the most common cause of blood infections and meningitis in newborns and is a frequent cause of newborn pneumonia. It is one of the leading causes in neonatal infections. Under the Centers for Disease Control (CDC) guidelines, pregnant women are screened for GBS at 35-37 weeks of gestation. Women positive for GBS are treated with β-lactam antibiotics, such as penicillin, four hours prior to delivery (Gibbs et al., 2004; Schrag et al., 2002).
In addition to pregnant women and infants, GBS also afflicts others, such as the elderly and those having underlying conditions such as diabetes or a compromised immune defense (Sendi et al., 2008).
Penicillin treatment appears effective in most incidents for GBS, and no cases of penicillin resistance have been reported. However, despite the penicillin treatment, GBS is occasionally found as evidenced by positive culture assay. This is attributed to penicillin tolerance (PT). GBS, when penicillin tolerant, exhibits growth inhibition during the penicillin treatment; but escapes to become viable when penicillin is taken off the treatment regimen. Using a culture and plating system to measure viability, Betriu et al. (1994) has reported that ˜17% of the clinical isolates demonstrate PT phenotype. Little is known about this PT phenotype behavior in GBS, let alone its underlying mechanisms. Currently, there is no screening test for PT in GBS, thus useful information is unavailable to improve current penicillin treatment (such as prolonging administration of penicillin).
The bactericidal action of penicillin occurs in two steps. The first step is the inhibition of growth via the binding of penicillin to the penicillin binding proteins (PBPs). The second step is the cidal step in which bacterial lytic enzymes are upregulated and secreted which subsequently disrupts the membrane potential and triggers autolysis. At least seven (7) PBPs have been found on the cell wall of bacteria and they share co-ordinate activities in cell wall synthesis. Different PBPs possess different biological properties. For example, PBP1a, 1b, 2a, and 2b contain structural domains essential in sugar synthesis and peptide linkage, whereas PBP4 is a D-alanyl-D-alanine carboxypeptidase (Macheboeuf et al., 2006).
It has been hypothesized that PT is a result of disconnection between the first step and the second step. Accordingly, PT converts penicillin from a bactericidal drug to a bacterial static drug. In other bacterial species such as Staphylococcus aureus and Streptococcus pneumoniae, it is suggested that PT in these species may be related to alterations in gene expression; more particularly, increased expression of lrgAB or lytSR may result in a penicillin tolerance phenotype (Rice and Bayles, 2008). Accordingly, there is a continuing need to provide a specific screening test for penicillin tolerance in Group B Streptococcus in mammals.